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Uncertainties in volume delineation in radiation oncology: A systematic review and recommendations for future studies

BACKGROUND AND PURPOSE Volume delineation is a well-recognised potential source of error in radiotherapy. Whilst it is important to quantify the degree of interobserver variability (IOV) in volume delineation, the resulting impact on dosimetry and clinical outcomes is a more relevant endpoint. We performed a literature review of studies evaluating IOV in target volume and organ-at-risk (OAR) delineation in order to analyse these with respect to the metrics used, reporting of dosimetric consequences, and use of statistical tests. METHODS AND MATERIALS Medline and Pubmed databases were queried for relevant articles using keywords. We included studies published in English between 2000 and 2014 with more than two observers. RESULTS 119 studies were identified covering all major tumour sites. CTV (n=47) and GTV (n=38) were most commonly contoured. Median number of participants and data sets were 7 (3-50) and 9 (1-132) respectively. There was considerable heterogeneity in the use of metrics and methods of analysis. Statistical analysis of results was reported in 68% (n=81) and dosimetric consequences in 21% (n=25) of studies. CONCLUSION There is a lack of consistency in conducting and reporting analyses from IOV studies. We suggest a framework to use for future studies evaluating IOV.

A review of interventions to reduce inter‐observer variability in volume delineation in radiation oncology

Inter‐observer variability (IOV) in target volume and organ‐at‐risk (OAR) delineation is a source of potential error in radiation therapy treatment. The aims of this study were to identify interventions shown to reduce IOV in volume delineation.

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

There is substantial interest in implementation of image‐guided intensity‐modulated radiotherapy (IG‐IMRT) in the post‐prostatectomy setting. We describe our implementation of IG‐IMRT, and examine how often published organ‐at‐risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol.

Assessment of serial multi-parametric functional MRI (diffusion-weighted imaging and R2∗) with (18)F-FDG-PET in patients with head and neck cancer treated with radiation therapy

OBJECTIVE To evaluate the serial changes and correlations between readout-segmented technique with navigated phase correction diffusion-weighted MRI (DWI), R2*-MRI and (18)F-FDG positron emission tomography (PET) CT performed before and during radiation therapy (RT) in patients with mucosal primary head and neck cancer. METHODS The mean apparent diffusion coefficient (ADCmean) from DWI (at b = 50 and 800 s mm(-2)), the mean R2* values derived from T2(*)-MRI, and PET metabolic parameters, including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) were measured for the primary tumour. Spearman correlation coefficients were calculated to evaluate correlations between ADCmean, R2*, SUVmax, MTV and TLG. A paired t-test was performed to assess the MRI changes and the slope of serial MRI changes during RT. RESULTS Pre-treatment scans were performed in 28 patients and mid-treatment scans in 20 patients. No significant correlation was found between ADCmean and either R2* values or PET parameters. There were significant negative correlations of R2* values with pre-treatment PET parameters but not with mid-RT PET parameters: pre-SUVmax (p = 0.008), pre-MTV (p = 0.006) and pre-TLG (p = 0.008). A significant rise in ADCmean was found during the first half (p < 0.001) of RT but not in the second half (p = 0.215) of the treatment. There was an increase of the ADCmean values of 279.4 [95% confidence interval (95% CI): 210-348] in the first half of the treatment (Weeks 0-3). However, during the second-half period of treatment, the mean ADC value (Weeks 3-6) was 24.0 and the 95% CI (-40 to 88) included zero. This suggests that there was no significant change in ADC values during the second half of the treatment. CONCLUSION A significant negative correlation was found between pre-treatment R2*-MRI and PET parameters. DWI appeared to demonstrate potentially predictable changes during RT. ADVANCES IN KNOWLEDGE Understanding the correlation and changes that occur with time between potential imaging biomarkers may help us establish the most appropriate biomarkers to consider in future research.

Prognostic utility of 18F-FDG PET-CT performed prior to and during primary radiotherapy for nasopharyngeal carcinoma: Index node is a useful prognostic imaging biomarker site

PURPOSE To evaluate the prognostic value of (18)F-FDG-PET-CT performed prior to (prePET) and during the third week (iPET) of radiation therapy (RT) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS Thirty-patients with newly diagnosed loco-regionally advanced NPC treated with radical RT underwent prePET and iPET. The median follow-up was 26months (8-66.9). The maximum-standardised-uptake-value (SUVmax), metabolic-tumour-volume (MTV) and total-lesional-glycolysis (TLG) of the primary tumour (PT), index-node (IN) (lymph node with highest TLG), total-lymph-nodes (TN) and combined primary-tumour and nodal (PTN), and their % reductions in iPET were analysed, and results were correlated with 2-year Kaplan-Meier loco-recurrence-free-survival (LRFS), regional-failure-free-survival (RFFS), distant-metastatic-failure-free-survival (DMFFS), disease-free-survival (DFS), and overall-survival (OS). Optimal-cutoffs (OC) were derived from Receiver-Operating-Characteristic curves. RESULTS For LRFS, the only predictor was reduction in PT MTV by >50%: 95.2% vs. 75.0%, p=0.024. For other treatment outcomes, only nodal or PTN predicted outcomes. The IN SUVmax (pre-PET-OC=10.45g/mL and iPET-OC=8.15) and TLG (prePET-OC=90g and iPET-OC=33.4) were the best predictors of outcome: RFFS (iPET SUVmax/TLG): 100% vs. 50%, p<0.001 and 100% vs. 44%, p=0.032; DMFFS (prePET SUVmax/TLG); 100% vs. 51.9%, p=0.004 and 100% vs. 47.6%, p=0.002; DFS (prePET TLG and iPET SUVmax): 87.5% vs. 33%, p=0.045 and 78.7% vs. 20%, p=0.01; and OS (prePET TLG): 100% vs 66.3%, p=0.036. CONCLUSIONS We have demonstrated IN of prePET and iPET to be a feasible and potentially useful novel imaging biomarker to predict for patients with NPC who have a high risk of regional or distant metastatic failure. Future work is required to validate our findings in a well-powered, prospective study with a standardised treatment protocol, and their potential use to guide individualised therapy for NPC.

A review of the predictive role of functional imaging in patients with mucosal primary head and neck cancer treated with radiation therapy

Advanced radiotherapy techniques, such as intensity‐modulated radiotherapy, have been reported to reduce toxicities by improving the dose conformity in mucosal primary head and neck cancer (MPHNC). However, to further optimize the therapeutic ratio, details on individual patient and disease characteristics may be necessary to tailor treatments. This is likely to include identifying poor responders for treatment intensification and good responders for de‐escalation strategies. Non‐invasive, repeatable imaging biomarkers are attractive modalities in both pre‐treatment and intra‐treatment response prediction with a view to individualized treatment options. This review has assessed the current literature on the prognostic/predictive role of widely available functional imaging (FI) studies such as fMRI(functional magnetic resonance imaging), functional computed tomography (fCT) and positron‐emission‐tomography(PET). A literature search was carried out using Medline, Embase and PubMed. Studies were included if imaging was undertaken pre and/or during radiotherapy (with or without the addition of chemotherapy and/or surgery). A total of 99 relevant studies were identified: 14 fMRI, 10 fCT, 59 FDG‐PET and 16 non‐FDG‐PET studies. These articles were reviewed to identify imaging parameters demonstrating a correlation with patient outcome or a factor considered to impact on patient outcome and thus likely to be of potential predictive value in MPHNC and associated future radiotherapy treatment directions. Several studies have demonstrated that both pre‐treatment and mid‐treatment FDG‐PET is predictive of outcomes. However, further studies are required to confirm the role of other imaging studies including fMRI and PET using other tracers. There is large heterogeneity within and between published studies, including tumour sites, treatment options, outcome endpoints and parameters assessed. We propose a minimum set of factors that should be reported and make recommendations for studies evaluating the predictive utility in MPHNC.

18F-FDG PET–CT performed before and during radiation therapy of head and neck squamous cell carcinoma : are they independent or complementary to each other?

The aims of this study are to evaluate the prognostic value of metabolic parameters derived from 18F‐FDG PET‐CT performed before definitive radiation therapy (RT) (prePET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to assess the additive prognostic values of FDG PET‐CT performed during RT (iPET).

External evaluation of the Radiation Therapy Oncology Group brachial plexus contouring protocol: several issues identified.

The aims of the study were to evaluate interobserver variability in contouring the brachial plexus (BP) using the Radiation Therapy Oncology Group (RTOG)‐approved protocol and to analyse BP dosimetries.

Assessment of MRI image quality for various setup positions used in breast radiotherapy planning

This study investigates breast magnetic resonance imaging (MRI) image quality for 3 different breast radiotherapy positions (prone, supine flat and supine inclined) and associated choice of breast coils. Supine breast MRI has comparable image quality to prone breast MRI for the purposes of radiotherapy delineation for T2-weighted sequences.

Are staging investigations being overused in patients with low and intermediate risk prostate cancer

According to international best practice guidelines, staging abdominal and pelvic computed tomography (CTAP) and whole body bone scan (WBBS) are not recommended for asymptomatic low and intermediate‐risk prostate cancer. Despite this, many patients undergo these investigations. Our aim was to determine the rate and cost of scans being performed for this group of patients.